Flaviviridae Flashcards
Faviviridae virion properties
- spherical
- 40-60 nm diameter
- icosahedral symmetry
- lipid envelope
What is the genome type of flaviviridae?
Single stranded, positive sense RNA
What gives the virus high susceptibility in the environment?
Envelope
- naked viruses are more hardy in the environment
Positive sense RNA
Single strand RNA which encodes mRNA and protein
What are the 3 genera of flaviviridae?
- pestivirus (bovine viral diarrhea virus)
- flavivirus (yellow fever virus)
- hepacivirus (hepatitis C virus)
What are 4 species of pestivirus with animal health significance?
- bovine viral diarrhea virus 1
- bovine viral diarrhea virus 2
- classic swine fever virus
- border disease virus
Bovine viral diarrhea virus has ______ distribution
Worldwide
What are the 2 biotypes of viruses?
- cytopathic
- noncytopathic
Which biotypes are virulent in cattle?
Both biotypes
Only _______ strains induce persistent infection
Non-cytopathic
- non-cytopathic can mutate to cytopathic
What clinical disease results from bovine viral diarrhea virus?
Mucosal
Why are cytopathic biotypes not persistent?
They destroy the cell (and their environment) upon infectivity
Transmission and persistence strategies of BVD
- induction of persistently infected (PI) hosts that shed and transmit BVDV efficiently
- suppression of host’s immune system
- transmission by various direct and indirect routes
BVDV transmission
- direct contact and aerosols
- blood and secretions
- meat products
- mechanic vectors
- in utero infection!
What is the main determinant of fetal response?
TIming of infection!
- embryonic death: 0-50 days after conception
- fetal abortion/mummification: 50-100 days
- congenital defects: 100-150 days
- normal: 150-200 days
Immunocompetent
150-200 days after conception
Tolerance/persistent infection
Occurs when infection in utero between 80-125 days of pregnancy
Immune tolerance
Immune system is not responding because infection is too early for the immune system to recognize the foreign antigen
- aka: state of unresponsiveness for an antigen
- lymphocytes will not respond to an antigen if they meet that antigen early in fetal life
BVDV infection in susceptible immunocompetent nonpregnant cattle causes:
- subclinical infection
- bovine viral diarrhea
- infection in neonatal calves
- venereal infections
Subclinical infections causes _____ infections in adult cattle
70-90%
- mild fever and leukopenia
- development of neutralizing antibodies
Bovine viral diarrhea is produced by ______
Both biotypes
- infect cattle 6 months - 2 years old
- depression, ocular discharge, oral erosions, ulcerations
- diarrhea with high morbidity and low to moderate mortality
- lesions in coronary band and interdigital cleft
- decrease in milk production
Infection in neonatal calves
Rarely seen in calves younger than 6 months
- severe enteritis, sometimes fatal
Venereal infections
Semen in infected bulls contains virus (transient)
- semen quality may decrease (motility and morphologic abnormalities)
Seronegative cows inseminated with infective semen
Fail to conceive until they develop an immune response
Mucosal disease occurs with:
2 biotypes of BVDV present
- persistent infection with non-cytopathogenic virus
- clinical signs similar to BVD but more severe
- fever anorexia, profuse watery diarrhea, nasal discharge, erosive or ulcerative stomatitis, dehydration emaciation and death
Mucosal disease superinfection occurs with:
Cytopathogenic virus
Lesions
Acute BVD: erosive/ulcerative lesions in mouth, esophagus, forestomachs, abomasum and intestine
- discoloration of mucosal folds (hyperemia and hemorrhage)
- necrosis of lymphoid tissue (Peyer patches)
In utero infection may induce _________
Hypoplasia cerebellar
What are the rule outs for BVDV?
- rinderpest
- foot and mouth disease
- vesicular stomatitis
Laboratory testing
- viral isolation
- viral antigen detection
- RT-PCR
- ELISA
- ear notches
What laboratory test detects most persistently infected animals?
RT-PCR off an ear notch
Classic swine fever transmission
Main route of infection is oronasal by direct or indirect contact with infected pigs
- indirect via contaminated feed
Classic swine fever severity depends on:
- age of the animal
- virulence of the virus
Classic swine fever signs
- acute infection: fever, depression, anorexia, conjunctivitis
- neurological signs: staggering gait paresis, lethargic, circling, tremors, convulsions
What are the 3 forms of classic swine fever?
- peracute: kills young swine with no clinical signs
- subacute
- chronic: always fatal
____ and ______ forms by strains of moderate virulence
Subacute and chronic
Classic swine fever is a ______ virus that can replicate in any cell type
Pantropic
Typical skin hemorrhages of classic swine fever
Ears, tail, abdomen and the inner side of the limbs
- appear from second or third weeks after infection until death
Classic swine fever pathogenesis
Most common route by ingestion
- replication leads to hemorrhages and leucopenia
- disseminated intravascular coagulation, thrombosis
Primary viral replication occurs in ______
Tonsils
- goes systemically from here
- collect a tonsil specimen to detect and diagnose CSF
Secondary replication occurs in _______
Endothelial cells, lymphoid organs, bone marrow
CSF virus causes severe leukopenia and ________
Immunosuppression
- dysfunction of immune system
- antibodies may be temporarily detected in serum, but they are not able to eliminate the virus from the host
Lesions in the 3 forms of CSF
- peracute: may be no gross changes
- acute: generalized submucosal and subserosal petechial hemorrhages, congestion and infarction in spleen, liver, bone marrow, lungs
- subacute + chronic: necrotic ulceration of mucosa and LI
- chronic: exhaustion of lymphoid system, atrophy of thymus and germinal center
________ is also a lesion of CSF
Non suppurative encephalitis
Prenatal infections
Infection in early pregnancy may result in abortions and stillbirths, mummification and malformations
- infections between 50-70 days of pregnancy can lead to birth of persistently viremic piglets
- piglets shed large amounts of virus!!
Rule outs of CSF
- African swine fever
- erysipelas
- porcine reproductive and respiratory syndrome
- post weaning multisystemic wasting syndrome
- salmonella
- pasteurella
Recommended actions if CSF is suspected
Report immediately upon diagnosis or suspicion!!
CSF samples for lab testing
Should be sent under secure conditions and to authorized labs to prevent spread of disease
- blood or tissue samples from acute cases for virus isolation, antigen detection or nucleic acid detection
- tonsils, maxillary, submandibular and mesenteric lymph nodes, spleen, kidneys, distal part of ileum
Genus Flavivirus
Some viruses are arthropod-borne zoonotic pathogens
- mosquito-borne encephalitides complex
- tick borne virus complex
Arbovirus
Viruses transmitted to vertebrate hosts by blood sucking arthropod vectors
Flaviviruses with animal and human significance
- West Nile virus
- japanese encephalitis virus
- louping ill virus
- zika virus
West Nile Virus is a member of the ______
Japanese encephalitis virus group
WNV is serologically related to ______
St Louis encephalitis and Japanese encephalitis virus
WNV
Endemic in Africa, Asia Southern Europe and North America
- transmission of virus among wild birds by infected mosquitoes
What are important reservoirs for WNV?
Passerines
- jay, finches, grackles, sparrows, crows
Principal mosquito vectors in the USA
- Culex pipiens
- Culex restvans
WNV has been isolated from over ______
300 species of birds
What are the 2 groups of WNV birds?
- asymptomatic: carriers
- susceptible: crows, jays, magpies, house finches
- –> develop neurological disease
WNV correlates with decline of ________
North American bird population
Since 1999, US has suffered a decrease of _______
Crow population
WNV avian infection
Range from subclinical to fatal with variability among species
- neurological signs common
WNV lesions
- necrosis and enlargement of spleen and liver
- myocardial degeneration
- pancreatitis
WNV disease has been reported in _____ and _____
Ducks and geese (poultry)
_____, ______, and ______ are incompetent reservoirs
Psittaciformes, galliformes, columbiformes
What is an important factor in disease transmission of WNV?
Viremia
- minimal possibility of transmitting virus from bird to mosquito unless high viremia is present
In WNV, the mosquito becomes a ______
Biological vector, because it is also infected
Mammals are considered to be _______ carriers for WNV
Dead-end
- viremia and viral load in blood are not sufficient to transmit WNV back to the mosquito, ending the transmission cycle
What other animal species have been reported to show signs of WNV infection?
Horses
- also: goats, sheep, dog, wolf, alpaca, alligator, squirrels, crocodile, llama, cattle, seal, cat
Mammal infection with WNV
Most mammals are do not play a role in enzootic transmission
- horses: depression, abnormal gait, ataxia, muscle tremors, recumbency
- dogs and cats: no illness!
- humans: neuroinvasive or non-neuroinvasive form (similar to flu)
West Nile Virus vaccine is available for ______
Horses
Rule outs for WNV in horses
- eastern equine encephalitis
- venezuelan equine encephalitis
- St. Louis equine encephalitis
- equine herpesvirus
- equine protozoal myeloencephalitis
WNV diagnosis
- RT-PCR
- IgM capure ELISA (acute infection)
Japanese encephalitis
Infects swine, horses, dogs, chickens, ducks, reptile, humans
- important disease for travelers
- fewer than 1 case/year in US citizens traveling to Asia
Japanese encephalitis symptoms
- horses: encephalitis
- swine: subclinical with abortions stillbirth, and aspermia
- humans: leading cause of encephalitis in Asia, diarrhea, headache, myalgia, paralysis, seizures, vomiting
Japanese encephalitis vector
Culex tritaeniorhynchus
Louping ill virus
Important in sheep
- seen in Europe
- neurological signs, hopping (louping) gait, nonsuppurative meningitis and encephalomyelitis
Louping ill virus vector
Tick borne
- Ixodes ricinus
- Rhipicephalus appendiculatus
- humans infected via tick bites or by contact with the virus in tissues or lab cultures
Flavivirus in humans
- Yellow fever
- St. Louis encephalitis
- Dengue
- Zika virus
Zika virus is a member of the ________
Spondweni virus group
- primarily through the bite of an infected Aedes mosquito
- illness is mild (symptoms last days to a week)
- fever, rash, joint pain, conjuctivitis, muscle pain, headaches
Zika virus in Brazil
Reports of microcephaly and poor pregnancy outcomes in mothers who were infected with Zika virus while pregnant
